NCT04607837: GLADIATOR UC

Etrasimod Versus Placebo for the Treatment of Moderately Active Ulcerative Colitis

Completed Phase 2 Results posted Last updated 15 July 2025

What this trial tests

Phase 2 trial testing Etrasimod in Ulcerative Colitis in 234 participants. Completed in 19 June 2024.

Timeline

12 April 2021

Primary endpoint
19 June 2024

19 June 2024

Quick facts

Lead sponsor	Pfizer
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	234
Start date	12 April 2021
Primary completion	19 June 2024
Estimated completion	19 June 2024
Sites	288 locations across Georgia, France, Italy, Russia, Ukraine, Belgium, Germany, Hungary

Drugs / interventions tested

• Etrasimod (ETRASIMOD) — full drug profile →
• Placebo

Conditions studied

• Ulcerative Colitis — all drugs for Ulcerative Colitis →

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 80, any sex, with Ulcerative Colitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving Clinical Remission (CR) at Week 52 Using Modified Mayo Score (MMS) Primary · Week 52

MMS is used to assess disease activity in participants with UC and has following components: endoscopic score(ES),rectal bleeding(RB),stool frequency(SF).Each component score ranges from 0 to 3(0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease.ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy,scores ranged from 0(normal or inactive disease) to 3(severe disease \[spontaneous bleeding, ulceration\]).RB reported most severe amount of blood passed per rectum in 24-hour period,scores ranged from 0(no blood seen) to 3(blood alone passes)

Group	Value	95% CI
Etrasimod	26.0
Placebo	18.3

Percentage of Participants Achieving Clinical Remission at Week 12 Using MMS Secondary · Week 12

MMS is used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe); higher scores indicating more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, scores ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]). RB reported the most severe amount of blood passed per rectum in a 24-hour period, scores ranged from 0 (no blood seen) to 3 (blood alone passes). SF reported number of stoo

Group	Value	95% CI
Etrasimod	28.3
Placebo	11.7

Percentage of Participants Achieving Endoscopic Improvement at Week 52 Secondary · Week 52

Endoscopic improvement was defined as ES \<=1 (excluding friability). ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. Percentage of participants achieving endoscopic improvement at Week 52 was evaluated in this endpoint.

Group	Value	95% CI
Etrasimod	32.3
Placebo	23.3

Percentage of Participants Achieving Symptomatic Remission at Week 52 Secondary · Week 52

Symptomatic remission was defined as SF =0 (or = 1 with a \>= 1 point decrease from baseline) and RB =0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving symptomatic remissio

Group	Value	95% CI
Etrasimod	37.0
Placebo	30.0

Percentage of Participants Achieving Complete Symptomatic Remission at Week 52 Secondary · Week 52

Complete symptomatic remission was defined as participants with RB = 0 and SF = 0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, scores ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. Percentage of participants achieving complete symptomatic remission at Week 52

Group	Value	95% CI
Etrasimod	20.5
Placebo	20.0

Percentage of Participants Achieving Histologic-Endoscopic Mucosal Improvement at Week 52 Secondary · Week 52

Histologic-endoscopic mucosal improvement was defined as ES \<=1 (excluding friability) with Geboes score \<2.0. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease \[spontaneous bleeding, ulceration\]), higher scores = more severity. The Geboes score grading system was a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade

Group	Value	95% CI
Etrasimod	25.2
Placebo	15.0

Percentage of Participants Achieving Clinical Remission at Both Weeks 12 and 52 [Combined] Using MMS Secondary · Weeks 12 and 52 [Combined]

MMS is used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0= normal, 1= mild, 2= moderate, 3= severe); higher scores = more severe disease. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease). RB: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes). SF reported number of stools in a 24-hour period relative to normal n

Group	Value	95% CI
Etrasimod	16.5
Placebo	5.0

Percentage of Participants With 12-Week Corticosteroid-Free Clinical Remission at Week 52 Among Participants Receiving Corticosteroids at Baseline Using MMS Secondary · Week 52

MMS has following components:ES, RB and SF. Each component score ranges from 0 to 3(0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease. ES:worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease)to 3(severe disease). RB:most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen)to 3(blood alone passes). SF:number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0(normal number of stools)

Group	Value	95% CI
Etrasimod	16.2
Placebo	16.7

Percentage of Participants With 12-Week Corticosteroid-Free Clinical Remission at Week 52 Using MMS Secondary · Week 52

MMS has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease. ES: worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease) to 3 (severe disease). RB: most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen) to 3 (blood alone passes). SF: number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0(normal number o

Group	Value	95% CI
Etrasimod	25.2
Placebo	16.7

Percentage of Participants Achieving 4-Week Corticosteroid-Free Clinical Remission at Week 52 Among Participants Receiving Corticosteroids at Baseline Using MMS Secondary · Week 52

MMS has following components: ES, RB and SF; each ranged as 0=normal,1=mild,2=moderate,3=severe; total MMS score 0-9; higher scores=more severe disease. ES:worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease)to 3(severe disease). RB:most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen) to 3(blood alone passes). SF:number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0(normal number of stools)to 3(5 or more

Group	Value	95% CI
Etrasimod	30.0
Placebo	30.0

Percentage of Participants With 4-Week Corticosteroid-Free Clinical Remission at Week 52 Using MMS Secondary · Week 52

MMS has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0=normal,1=mild,2=moderate,3=severe); where total score is sum of three components giving total MMS score as 0 to 9; higher scores indicating more severe disease. ES: worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0(normal or inactive disease) to 3 (severe disease). RB: most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0(no blood seen) to 3 (blood alone passes). SF: number of stools in a 24-hour period relative to normal number of stoo

Group	Value	95% CI
Etrasimod	25.2
Placebo	16.7

Percentage of Participants Achieving Clinical Response at Week 12 Using MMS Secondary · Week 12

Clinical response was defined as a \>=2-point and \>=30 percentage (%) decrease from baseline in MMS, and a \>=1-point decrease from baseline in RB subscore or an absolute RB subscore \<=1 and is as per FDA draft guidance. MMS was used to assess disease activity in participants with UC and has following components: ES, RB and SF. Each component score ranges from 0 to 3 (0= normal, 1= mild, 2= moderate, 3= severe); where total score is sum of three components giving total MMS score as 0 to 9; higher scores indicating more severe disease. ES reported worst appearance of mucosa on flexible sigmoi

Group	Value	95% CI
Etrasimod	55.9
Placebo	36.7

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study treatment up to 4 weeks post last dose of study treatment (up to 56 Weeks). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Etrasimod

Serious: 10/154 (6%)

Deaths: 0/154

Placebo

Serious: 1/79 (1%)

Deaths: 0/79

Serious adverse events (10 terms)

Reaction	System	Etrasimod	Placebo
Colitis ulcerative	Gastrointestinal disorders	—	—
Chest pain	General disorders	—	—
Cholelithiasis	Hepatobiliary disorders	—	—
Post procedural infection	Infections and infestations	—	—
Viral infection	Infections and infestations	—	—
Incisional hernia	Injury, poisoning and procedural complications	—	—
Radius fracture	Injury, poisoning and procedural complications	—	—
Ulna fracture	Injury, poisoning and procedural complications	—	—
Epilepsy	Nervous system disorders	—	—
Angioedema	Skin and subcutaneous tissue disorders	—	—

Other adverse events (191 terms — click to expand)

Reaction	System	Etrasimod	Placebo
Colitis ulcerative	Gastrointestinal disorders	—	—
COVID-19	Infections and infestations	—	—
Alanine aminotransferase increased	Investigations	—	—
Gamma-glutamyltransferase increased	Investigations	—	—
Headache	Nervous system disorders	—	—
Aspartate aminotransferase increased	Investigations	—	—
Blood triglycerides increased	Investigations	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Fatigue	General disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Blood creatine phosphokinase increased	Investigations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Influenza	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Large intestine polyp	Gastrointestinal disorders	—	—
Influenza like illness	General disorders	—	—
Conjunctivitis	Infections and infestations	—	—
Activated partial thromboplastin time prolonged	Investigations	—	—
Blood alkaline phosphatase increased	Investigations	—	—
Blood cholesterol increased	Investigations	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—
Somnolence	Nervous system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Hypertension	Vascular disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Bradycardia	Cardiac disorders	—	—
Sinus bradycardia	Cardiac disorders	—	—
Tinnitus	Ear and labyrinth disorders	—	—
Cataract	Eye disorders	—	—
Abdominal pain lower	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Rectal haemorrhage	Gastrointestinal disorders	—	—

Most-reported serious reactions: Colitis ulcerative, Chest pain, Cholelithiasis, Post procedural infection, Viral infection, Incisional hernia, Radius fracture, Ulna fracture.

Data from ClinicalTrials.gov NCT04607837 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether oral etrasimod is a safe and effective treatment for moderately active ulcerative colitis in adult participants.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. A review of the therapeutic management of ulcerative colitis.
   Aslam N, Lo SW, Sikafi R, Barnes T, et al · · 2022 · cited 46× · PMID 36478780 · DOI 10.1177/17562848221138160
2. Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management.
   Kitsou K, Kokkotis G, Rivera-Nieves J, Bamias G. · · 2024 · cited 22× · PMID 39322927 · DOI 10.1007/s40265-024-02094-5
3. Immunity in digestive diseases: new drugs for inflammatory bowel disease treatment-insights from Phase II and III trials.
   Massironi S, Furfaro F, Bencardino S, Allocca M, et al · · 2024 · cited 19× · PMID 38980426 · DOI 10.1007/s00535-024-02130-x
4. How sphingolipids affect T cells in the resolution of inflammation.
   Hartel JC, Merz N, Grösch S. · · 2022 · cited 17× · PMID 36176439 · DOI 10.3389/fphar.2022.1002915
5. UEG Week 2025 Oral Presentations
   · 2025